The effects of potassium-ATP channel modulation on ventricular fibrillation and defibrillation in the pig heart

Background: Drugs acting on the cardiac ATP-sensitive potassium (K-ATP) cha nnels may modulate responses to ischaemia and arrhythmogenesis. We investig ated the effects of K-ATP channel modulation on frequency patterns of ventr icular fibrillation (VF) and on defibrillation threshold (DFT). Methods and Results: Each group of 24 pigs randomly received intravenous levcromakalim (LKM) 40 mug/kg (K-ATP agonist), glibenclamide (Glib) 20 mg/kg (K-ATP anta gonist); saline or vehicle. Firstly, QTc interval was measured before and a fter drug. VF was then induced by endocardial stimulation and its power spe ctra and dominant frequencies over 15 min determined by fast Fourier transf ormation. Secondly, transthoracic DFT was determined (step-up/step-down pro tocol) before and after each drug. LKM reduced QTc interval (e.g., lead II, 354-321 ms, P<0.05) and increased the dominant VF frequency between 6 and 8 min (9.5+/-0.5 Hz at 6.5 min compared with 7.2+/-0.6 Hz (saline), 7.4+/-0 .8 Hz (vehicle), 6.8-0.5 Hz (Glib), P=0.03): LKM reduced (to 57.2+/-2.1 mmH g) and Glib increased (to 107.8+/-6.1) mean arterial BP compared with salin e (80.3+/-5.6) and vehicle (87.6+/-7.1; P<0.01). There was no significant d ifference in defibrillation threshold energy, current or voltage, after any drug. Conclusions: Activation of K-ATP channels reduced blood pressure and QTc interval. The lack of major effect on VF dominant frequency and DFT of either LKM or Glib suggests that prior administration of similar drugs to patients should not prejudice outcome from VF cardiac arrest. (C) 2000 Else vier Science Ireland Ltd. All rights reserved.